The overall theme of the renewal application is to continue the studies of the consequences of disorders of fetal metabolism on the mother and the newborn infant while at the same time obtaining normative data in humans describing the adaptive response of the mother during pregnancy. Gestational diabetes has been chosen as the model for study in humans because (i) it constitutes by far the largest group of pregnant women with abnormalities of carbohydrate metabolism, (ii) the evolution of metabolic aberrations can be sequenced as gestation advances, and (iii) the intervention strategies car be more rigorously evaluated. Clinical studies of gestational diabetes will define an defect the abnormalities in glucose tolerance early in gestation and relate these to perinatal outcome. Therapeutic regimens will be evaluated for their efficacy and their effectiveness in relation to time of gestation. The normal adaptive responses in pregnancy in relation to glucose utilization will be examined using stable isotopic tracer and mass spectrometry methods. The effect of diabetes and its management on maternal and neonatal protein, fat and energy metabolism will be quantified. In addition, the effect of maternal hyperglycemia on fetal cardiovascular function will be examined using the newer doppler methods in conjunction with glucose clamp technique. A new initiative is focused at defining the molecular mechanism by which cAMP might increase estrogen production in the human placenta. Other studies in newborn will examine the metabolic and hormonal changes associated with neonatal adaptation to extrauterine life and discover how newborn behaviors organization is influenced by changes in circulating fuels. In animals studies, the long term biochemical and morphometric consequences of neonatal nutrition perturbations will be evaluated. These studies will broaden the original theme of the PERC and improve our understanding of the metabolic and nutritional aberration of maternal fetal and neonatal physiology and will help in the management of clinical problem in this population.